We will develop a noninvasive technique to measure strain on orthopedic plates in order to quantify the mechanical stiffness of bone fracture calluses and to assess the effectiveness of osteoinductive treatments. Over 28 million musculoskeletal injuries are treated annually in the US including 2 million fracture-fixation surgeries. Limb fractures with large segmental defects are especially challenging to treat and have high rates of non-union and revision surgeries. A key goal in orthopedic research is to develop osteoinductive treatments (e.g., using BMPs, or periostin) to accelerate healing and reduce complication rates. To help researchers develop and optimize these regenerative treatments, and to help physicians evaluate healing in individual patients, there is an urgent need for techniques to quantify mechanical properties of fracture calluses in vivo. Although animal studies have used transcutaneously connected resistive strain gauges to measure decreasing plate strain during healing as the fracture callus stiffens and increasingly shares the load, the connecting wires would be infection risks and impractical for human patients. We will develop a novel, elegant, low-cost, sensitive, noninvasive, and highly versatile solution based on luminescence spectroscopy. While optical displacements are commonly measured in vitro via image analysis, our approach is novel in that we perform sensitive measurement through tissue by measuring spectral changes in essentially background-free, deeply penetrating upconversion luminescence. The measurements can be made using a portable spectrometer system for point-of-care measurements, and the gauges have a low profile for simple incorporation into or onto existing plates. We will calibrate the sensor by measuring the luminescence spectrum as a function of load (4- point bending and axial compression) in a plated tibia-equivalent specimen and evaluate strain sensitivity through various tissue thicknesses. We will then implant a titanium dynamic-compression plate with a luminescent strain gauge into 4 groups of rabbits in a tibial osteotomy model with varying defect sizes to control healing rate. We will measure the implant strain in each group over a period of 6 weeks and compare results with in vivo ?-CT in the Bioengineering and Bioimaging Core, as well as histology in the Cell, Tissue, and Molecular Analyses Core. We will then repeat the experiments for rabbits treated with osteogenic molecules (BMP-2 or periostin) and compare results with untreated animals. Our strong interdisciplinary team, consisting of Dr. Anker (PI), Dr. DesJardins (biomechanical collaborator), Dr. Chip Norris (another targeted COBRE PI developing osteoinductive periostin treatments), Dr. Tom Pace (orthopedic surgeon and clinical mentor), and academic advisors Drs. Bob Latour, Roger Markwald, and Naren Vyavahare, will bring this innovative technology from a novel spectroscopic tool to a noninvasive sensor to assess in vivo bone healing.